Subdivision of the Drosophila wing imaginal disc by EGFR-mediated signaling

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1357-1368 ◽  
Author(s):  
Myriam Zecca ◽  
Gary Struhl
Keyword(s):  
Imaginal Disc ◽  
Growth Factor Receptor ◽  
Subsequent Development ◽  
Wing Disc ◽  
Wing Imaginal Disc ◽  
Egfr Signaling ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Epidermal Growth ◽  
Necessary And Sufficient

Growth and patterning of the Drosophila wing imaginal disc depends on its subdivision into dorsoventral (DV) compartments and limb (wing) and body wall (notum) primordia. We present evidence that both the DV and wing-notum subdivisions are specified by activation of the Drosophila Epidermal Growth Factor Receptor (EGFR). We show that EGFR signaling is necessary and sufficient to activate apterous (ap) expression, thereby segregating the wing disc into D (ap-ON) and V (ap-OFF) compartments. Similarly, we demonstrate that EGFR signaling directs the expression of Iroquois Complex (Iro-C) genes in prospective notum cells, rendering them distinct from, and immiscible with, neighboring wing cells. However, EGFR signaling acts only early in development to heritably activate ap, whereas it is required persistently during subsequent development to maintain Iro-C gene expression. Hence, as the disc grows, the DV compartment boundary can shift ventrally, beyond the range of the instructive EGFR signal(s), in contrast to the notum-wing boundary, which continues to be defined by EGFR input.

Control of growth and patterning of the Drosophila wing imaginal disc by EGFR-mediated signaling

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1369-1376 ◽  
Author(s):  
Myriam Zecca ◽  
Gary Struhl
Keyword(s):  
Gene Expression ◽  
Imaginal Disc ◽  
Ectopic Expression ◽  
Growth Factor Receptor ◽  
Wing Disc ◽  
Wing Imaginal Disc ◽  
Egfr Signaling ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Egfr Ligand

The subdivision of the Drosophila wing imaginal disc into dorsoventral (DV) compartments and limb-body wall (wing-notum) primordia depends on Epidermal Growth Factor Receptor (EGFR) signaling, which heritably activates apterous (ap) in D compartment cells and maintains Iroquois Complex (Iro-C) gene expression in prospective notum cells. We examine the source, identity and mode of action of the EGFR ligand(s) that specify these subdivisions. Of the three known ligands for the Drosophila EGFR, only Vein (Vn), but not Spitz or Gurken, is required for wing disc development. We show that Vn activity is required specifically in the dorsoproximal region of the wing disc for ap and Iro-C gene expression. However, ectopic expression of Vn in other locations does not reorganize ap or Iro-C gene expression. Hence, Vn appears to play a permissive rather than an instructive role in organizing the DV and wing-notum segregations, implying the existance of other localized factors that control where Vn-EGFR signaling is effective. After ap is heritably activated, the level of EGFR activity declines in D compartment cells as they proliferate and move ventrally, away from the source of the instructive ligand. We present evidence that this reduction is necessary for D and V compartment cells to interact along the compartment boundary to induce signals, like Wingless (Wg), which organize the subsequent growth and differentiation of the wing primordium.

scholarly journals msh specifies dorsal cell fate in the Drosophila wing

Development ◽  
2001 ◽  
Vol 128 (17) ◽  
pp. 3263-3268 ◽  
Author(s):  
Marco Milán ◽  
Ulrich Weihe ◽  
Stanley Tiong ◽  
Welcome Bender ◽  
Stephen M. Cohen
Keyword(s):  
Cell Fate ◽  
Imaginal Disc ◽  
Homeobox Gene ◽  
Wing Imaginal Disc ◽  
Wing Development ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Signaling Center ◽  
Dorsal Cells ◽  
Dorsal Cell Fate

Drosophila limbs develop from imaginal discs that are subdivided into compartments. Dorsal-ventral subdivision of the wing imaginal disc depends on apterous activity in dorsal cells. Apterous protein is expressed in dorsal cells and is responsible for (1) induction of a signaling center along the dorsal-ventral compartment boundary (2) establishment of a lineage restriction boundary between compartments and (3) specification of dorsal cell fate. Here, we report that the homeobox gene msh (muscle segment homeobox) acts downstream of apterous to confer dorsal identity in wing development.

scholarly journals Regulated delivery controls Drosophila Hedgehog, Wingless and Decapentaplegic signaling

2020 ◽  
Author(s):  
Ryo Hatori ◽  
Thomas B. Kornberg
Keyword(s):  
Signal Transduction ◽  
Imaginal Disc ◽  
Wing Disc ◽  
Bone Morphogenic Protein ◽  
Wing Imaginal Disc ◽  
Target Cells ◽  
Signaling Proteins ◽  
Common Pool ◽  
Drosophila Wing ◽  
Disc Cells

AbstractMorphogen signaling proteins disperse across tissues to activate signal transduction in target cells. We investigated dispersion of Hedgehog (Hh), Wingless (Wg), and Bone morphogenic protein homolog Decapentaplegic (Dpp) in the Drosophila wing imaginal disc, and found that delivery to targets is regulated. Cells take up <5% Hh produced, and neither amounts taken up nor extent of signaling changes under conditions of Hh production from 50-200% normal amounts. Similarly, cells take up <25% Wg produced, and variation in Wg production from 50-700% normal has no effect on amounts taken up or signaling. Similar properties were observed for Dpp. Wing disc-produced Hh signals to disc-associated tracheal and myoblast as well as an approximately equal number of disc cells, but the extent of signaling in the disc is unaffected by the presence or absence of the tracheal cells and myoblasts. These findings show that target cells do not take up signaling proteins from a common pool and that both the amount and destination of delivered morphogens are regulated..SummaryThe extent of Hh, Wg, and Dpp signaling is independent of the amount of signal produced or the number of recipient cells.

A dual role for homothorax in inhibiting wing blade development and specifying proximal wing identities in Drosophila

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1499-1508 ◽  
Author(s):  
F. Casares ◽  
R.S. Mann
Keyword(s):  
Signal Transduction ◽  
Imaginal Disc ◽  
Target Genes ◽  
Notch Pathway ◽  
Wing Disc ◽  
Signal Transduction Pathways ◽  
Body Parts ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Three Body

The Drosophila wing imaginal disc gives rise to three body parts along the proximo-distal (P-D) axis: the wing blade, the wing hinge and the mesonotum. Development of the wing blade initiates along part of the dorsal/ventral (D/V) compartment boundary and requires input from both the Notch and wingless (wg) signal transduction pathways. In the wing blade, wg activates the gene vestigial (vg), which is required for the wing blade to grow. wg is also required for hinge development, but wg does not activate vg in the hinge, raising the question of what target genes are activated by wg to generate hinge structures. Here we show that wg activates the gene homothorax (hth) in the hinge and that hth is necessary for hinge development. Further, we demonstrate that hth also limits where along the D/V compartment boundary wing blade development can initiate, thus helping to define the size and position of the wing blade within the disc epithelium. We also show that the gene teashirt (tsh), which is coexpressed with hth throughout most of wing disc development, collaborates with hth to repress vg and block wing blade development. Our results suggest that tsh and hth block wing blade development by repressing some of the activities of the Notch pathway at the D/V compartment boundary.

scholarly journals Hedgehog produced by the Drosophila wing imaginal disc induces distinct expression responses in three target tissues

2020 ◽  
Author(s):  
Ryo Hatori ◽  
Thomas B. Kornberg
Keyword(s):  
Imaginal Disc ◽  
Wing Disc ◽  
Wing Imaginal Disc ◽  
Cell Type ◽  
Concentration Gradients ◽  
Anterior Compartment ◽  
Animal Development ◽  
Drosophila Wing ◽  
Evolutionarily Conserved ◽  
Cell Type Specific

AbstractHedgehog (Hh) is an evolutionarily conserved signaling protein that has essential roles in animal development and homeostasis. We investigated Hh signaling in the region of the Drosophila wing imaginal disc that produces Hh and is near the tracheal air sac primordium (ASP) and myoblasts. Hh distributes in concentration gradients in the wing disc anterior compartment, ASP, and myoblasts and activates different sets of genes in each tissue. Some transcriptional targets of Hh signal transduction are common to the disc, ASP, and myoblasts, whereas others are tissue-specific. Signaling in the three tissues is cytoneme-mediated and cytoneme-dependent. We conclude that a single source of Hh in the wing disc regulates cell type-specific responses in three discreet target tissues.SummaryHedgehog produced by the wing imaginal disc signals to wing disc, myoblast and tracheal cells

scholarly journals Updated Insights on EGFR Signaling Pathways in Glioma

2021 ◽  
Vol 22 (2) ◽  
pp. 587
Author(s):  
Alexandru Oprita ◽  
Stefania-Carina Baloi ◽  
Georgiana-Adeline Staicu ◽  
Oana Alexandru ◽  
Daniela Elise Tache ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Egfr Signaling ◽  
Current Standard ◽  
Egfr Amplification ◽  
Epidermal Growth ◽  
New Diagnosis ◽  
Clear Clinical Benefit

Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.

scholarly journals Dominant Enhancers of Egfr in Drosophila melanogaster: Genetic Links Between the Notch and Egfr Signaling Pathways

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1139-1153 ◽  
Author(s):  
James V Price ◽  
Edward D Savenye ◽  
David Lum ◽  
Ashton Breitkreutz
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Growth Factor Receptor ◽  
Compound Eyes ◽  
Egfr Signaling ◽  
Wing Vein ◽  
Developmental Context ◽  
Epidermal Growth ◽  
Hypomorphic Alleles ◽  
Complex Signaling

The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed and F1 screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context.

scholarly journals Mdm2-Mediated Downmodulation of GRK2 Restricts Centrosome Separation for Proper Chromosome Congression

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 729
Author(s):  
Clara Reglero ◽  
Belén Ortiz del Castillo ◽  
Verónica Rivas ◽  
Federico Mayor ◽  
Petronila Penela
Keyword(s):  
Hippo Pathway ◽  
Growth Factor Receptor ◽  
Receptor Kinase ◽  
Egfr Signaling ◽  
Polyubiquitin Chains ◽  
Centrosome Separation ◽  
Chromosome Congression ◽  
Epidermal Growth ◽  
The Hippo Pathway ◽  
G Protein Coupled

The timing of centrosome separation and the distance moved apart influence the formation of the bipolar spindle, affecting chromosome stability. Epidermal growth factor receptor (EGFR) signaling induces early centrosome separation through downstream G protein-coupled receptor kinase GRK2, which phosphorylates the Hippo pathway component MST2 (Mammalian STE20-like protein kinase 2), in turn allowing NIMA kinase Nek2A activation for centrosomal linker disassembly. However, the mechanisms that counterbalance centrosome disjunction and separation remain poorly understood. We unveil that timely degradation of GRK2 by the E3 ligase Mdm2 limits centrosome separation in the G2. Both knockout expression and catalytic inhibition of Mdm2 result in GRK2 accumulation and enhanced centrosome separation before mitosis onset. Phosphorylation of GRK2 on residue S670 enables a complex pattern of non-K48-linked polyubiquitin chains assembled by Mdm2, which correlate with kinase protein degradation. Remarkably, GRK2-S670A protein fails to phosphorylate MST2 despite overcoming Mdm2-dependent degradation, which results in defective centrosome separation, shorter spindles, and abnormal chromosome congression. Conversely, extra levels of wild-type kinase in the G2 cause increased inter-centrosome distances with longer spindles, also converging in congression issues. Our findings show that the signals enabling activity of the GRK2/MST2/Nek2A axis for separation also switches on Mdm2 degradation of GRK2 to ensure accurate centrosome dynamics and proper mitotic spindle functionality.

scholarly journals Compartments and the control of growth in the Drosophila wing imaginal disc

Development ◽  
2006 ◽  
Vol 133 (22) ◽  
pp. 4421-4426 ◽  
Author(s):  
F. A. Martin ◽  
G. Morata
Keyword(s):  
Imaginal Disc ◽  
Wing Imaginal Disc ◽  
Drosophila Wing
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